Ontogenic regulation of spatial differentiation in the crypt-villus axis of normal and isografted small intestine. Gutierrez, E. D., K. J. Grapperhaus, and D. C. Rubin. Division of Gastroenterology, Washington University School of Medicine and the Jewish Hospital of St. Louis.
APStracts 2:0061G, 1995.
Despite rapid proliferation, the mammalian intestinal epithelium maintains precise spatial differentiation from crypt-to-villus tip and from duodenum to colon. During perinatal life, the rodent gut undergoes a dramatic morphogenesis, resulting in formation of the crypt-villus and duodenal-colonic axes. The ontogeny of regional differences in gene expression in the emerging vertical axis has not been well-described. We used the liver fatty acid binding protein (L -FABP) and apolipoprotein (apo) AIV genes as markers of neonatal enterocytic differentiation. In situ hybridization analyses revealed that both genes exhibit unique spatial patterns of expression along the jejunal crypt-villus axis during ontogeny, characterized by increased cellular mRNA levels in villus base enterocytes. To examine the requirement for a normal luminal environment to generate these precise patterns of cellular gene expression, we employed intestinal isograft techniques. Fetal intestines were implanted as early as embryonic day (E) 12. Appropriate expression of the apo AIV and L -FABP genes was recapitulated during the initial period of villus morphogenesis during fetal life. However, spatial patterns of gene expression in the isografted postnatal crypt-villus axis were altered. The preferential accumulation of L-FABP and apo AIV mRNA in villus base enterocytes was never observed in isografts. These results suggest that a "basal" differentiation program is encoded in fetal endoderm and mesenchyme, yet extracellular substances contained in the lumen or extrinsic to the intestine play an important modulatory role in generating spatial differentiation during ontogeny. 

Received 26 September 1994; accepted in final form 29 March 1995.
APS Manuscript Number G374-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 19 April 1995.